PT1370556E - Inibidores de metaloproteinases - Google Patents
Inibidores de metaloproteinases Download PDFInfo
- Publication number
- PT1370556E PT1370556E PT02704031T PT02704031T PT1370556E PT 1370556 E PT1370556 E PT 1370556E PT 02704031 T PT02704031 T PT 02704031T PT 02704031 T PT02704031 T PT 02704031T PT 1370556 E PT1370556 E PT 1370556E
- Authority
- PT
- Portugal
- Prior art keywords
- alkyl
- apci
- nmr
- dialkylamino
- alkylamino
- Prior art date
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- 239000003475 metalloproteinase inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 208
- -1 arylheteroalkyl Chemical group 0.000 claims description 117
- 229910052739 hydrogen Inorganic materials 0.000 claims description 106
- 125000000217 alkyl group Chemical group 0.000 claims description 83
- 229910052757 nitrogen Inorganic materials 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 30
- 229910052717 sulfur Inorganic materials 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- 150000002148 esters Chemical class 0.000 claims description 29
- 238000001727 in vivo Methods 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 26
- 125000001072 heteroaryl group Chemical group 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 102000005741 Metalloproteases Human genes 0.000 claims description 23
- 108010006035 Metalloproteases Proteins 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 22
- 125000005842 heteroatom Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000004429 atom Chemical group 0.000 claims description 21
- 125000004122 cyclic group Chemical group 0.000 claims description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 15
- 125000001188 haloalkyl group Chemical group 0.000 claims description 15
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 125000006413 ring segment Chemical group 0.000 claims description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 125000005157 alkyl carboxy group Chemical group 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- 125000004419 alkynylene group Chemical group 0.000 claims description 8
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 8
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 8
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 7
- 125000003368 amide group Chemical group 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000006168 tricyclic group Chemical group 0.000 claims description 7
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 6
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- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
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- 150000007942 carboxylates Chemical class 0.000 claims description 4
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 2
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 45
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 28
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- 101000577881 Homo sapiens Macrophage metalloelastase Proteins 0.000 description 14
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- WUBVEMGCQRSBBT-UHFFFAOYSA-N tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(=O)(=O)C(F)(F)F)=CC1 WUBVEMGCQRSBBT-UHFFFAOYSA-N 0.000 description 1
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- RDBYGNSYOIZOJG-UHFFFAOYSA-N tert-butyl 4-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=C(OC(F)(F)F)C=C1 RDBYGNSYOIZOJG-UHFFFAOYSA-N 0.000 description 1
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- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
- C07D233/78—Radicals substituted by oxygen atoms
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DE60234028D1 (de) | 2001-05-25 | 2009-11-26 | Bristol Myers Squibb Co | Hydantion-derivate als hemmer von matrix-metalloproteinasen |
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2010
- 2010-01-26 US US12/693,852 patent/US8153673B2/en not_active Expired - Fee Related
- 2010-07-06 US US12/830,763 patent/US20110003853A1/en not_active Abandoned
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